Recognition of the usefulness of lithium carbonate in the treatment and prophylaxis of various forms of affective illness has prompted extensive new inquiries into its pharmacological actions as well as an examination of the characteristics of lithium responders and non-responders. In the course of examining the clinical effectiveness of treating depressed patients with lithium, we have tentatively concluded that a subgroup of depressed patients, probably manic-depressives, do respond to treatment with this compound. We have reported evidence that the depressed patients who respond accumulate significantly more lithium inside their erythrocytes than non-responders in spite of the fact that they receive the same dose of lithium and have similar plasma levels. This and related evidence has led us to tentatively conclude that there is some difference in the cell membrane characteristics governing the transport of lithium in patients who respond as compared with patients who do not respond to treatment with this element. Further exploration of this phenomenon is indicated. Among the projected plans are studies designed to confirm the initial findings and also to examine in general detail some of the characteristics of electrolyte transport systems into and out of the erythrocyte. An examination of some aspects of the neurophysiological implications of this is also planned.